Prophylactic potential of montelukast against mild colitis induced by dextran sulphate sodium in rats.

Abstract

Cysteinyl leukotrienes play a part in inflammatory processes such as inflammatory bowel diseases. The present study aimed to evaluate the effects of the cys-LT-1 receptor antagonist montelukast on a mild colitis model in rats. Colitis was induced by administrating 4% dextran sulphate sodium (DSS, MW 45,000) in drinking water for 9 days. Montelukast (10 mg/kg/day) or vehicle was given by gastric gavage once daily simultaneously with DSS administration. A healthy control group receiving water as drinking fluid and vehicle by gastric gavage was included. Body weight loss, consistency of faeces (loose/diarrhoea) and occult blood in the faeces/ gross bleeding were assessed on days 6 - 9. After sacrifice, the following were assessed: colonic histology, the expression of inducible nitric oxide synthase, macrophage/monocyte marker ED1, cyclooxygenase-1 and cyclooxygenase-2, as well as the production of leukotriene B(4) and E(4), prostaglandin E(2), its metabolite bicyclic-prostaglandin E(2) and thromboxane B(2) in the colonic tissue incubation in vitro. Rats receiving DSS exhibited bloody diarrhoea from day 6 onwards. Montelukast significantly reduced the occult blood in the faeces/ gross bleeding, maintained normal body weight gain and tended to decrease the ratio of leukotriene B(4)/ prostaglandin E(2) production in the colon in vitro. The results indicate that montelukast has some potential to ameliorate mild experimental colitis induced by DSS.

• Authors: R Holma, P Salmenperä, I Virtanen, H Vapaatalo, R Korpela
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 58 Issue 3 Pg. 455-67 (Sep 2007) ISSN: 0867-5910 [Print] Poland
• PMID: 17928642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Bridged Bicyclo Compounds
• Cyclopropanes
• Immunoglobulin G
• Leukotriene Antagonists
• Quinolines
• Sulfides
• Leukotriene B4
• Thromboxane B2
• Dextran Sulfate
• Nitric Oxide Synthase Type II
• Cyclooxygenase 1
• Cyclooxygenase 2
• Dinoprostone
• montelukast

Topics

• Acetates (administration & dosage, pharmacology, therapeutic use)
• Administration, Oral
• Animals
• Blotting, Western
• Body Weight (drug effects)
• Bridged Bicyclo Compounds (metabolism)
• Colitis (chemically induced, pathology, prevention & control)
• Colon (drug effects, metabolism, pathology)
• Cyclooxygenase 1 (metabolism)
• Cyclooxygenase 2 (metabolism)
• Cyclopropanes
• Dextran Sulfate (administration & dosage, toxicity)
• Dinoprostone (metabolism)
• Immunochemistry
• Immunoglobulin G (metabolism)
• Leukotriene Antagonists (administration & dosage, pharmacology, therapeutic use)
• Leukotriene B4 (metabolism)
• Male
• Nitric Oxide Synthase Type II (metabolism)
• Occult Blood
• Quinolines (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Severity of Illness Index
• Sulfides
• Thromboxane B2 (metabolism)